Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 26 220
Страница 747 из 1000-
CRISPR target prediction remains blunt tool for clinical applications.
-
Expanding Horizons of CRISPR/Cas Technology: Clinical Advancements, Therapeutic Applications, and Challenges in Gene Therapy.
CRISPR-Cas technology has transformed the field of gene editing, opening new possibilities for treatment of various genetic disorders. Recent years have seen a surge in clinical trials using CRISPR-Cas-based therapies. This review examines the current landscape of CRISPR-Cas implementation in clinical trials, with data from key registries, including the Australian New Zealand Clinical Trials Registry, the Chinese Clinical Trial Register, and ClinicalTrials.gov. Emphasis is placed on the mechanism of action of tested therapies, the delivery method, and the most recent findings of each clinical trial.
-
Precision Reimagined: CRISPR and Multiomics Transform Systemic Lupus Erythematosus Diagnosis and Therapy.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with diverse clinical manifestations and unpredictable progression, posing significant challenges to accurate diagnosis and effective treatment. Traditional biomarkers and treatments often fail to address the disease's molecular and clinical heterogeneity. Recent advancements in CRISPR gene-editing technology and multiomics approaches offer transformative opportunities for personalized SLE care by unraveling its underlying molecular complexity and enabling precise therapeutic interventions. CRISPR technology allows targeted editing of SLE-associated genetic mutations, addressing disease drivers directly, while multiomics-including genomics, transcriptomics, and proteomics-provides insights into dysregulated immune networks, identifying biomarkers and therapeutic targets. Integrating these approaches can refine patient stratification and enhance the precision of treatments. Artificial intelligence (AI) complements these technologies by synthesizing high-dimensional data, enabling personalized treatment plans, predicting disease trajectories, and optimizing therapeutic strategies. However, the integration of CRISPR and multiomics in clinical settings raises challenges, including technical limitations, ethical concerns, and economic barriers. Emerging clinical trials and case studies demonstrate the potential of these innovations to personalize care and improve outcomes. Nonetheless, the transition from experimental research to routine clinical application requires robust regulatory frameworks and strategies to address these challenges. This review aims to explore the potential of CRISPR and multiomics technologies to revolutionize SLE diagnosis and therapy, emphasizing their integration with AI to advance personalized care. By addressing existing barriers, the review envisions a future where precision medicine transforms SLE management, paving the way for individualized, patient-centered autoimmune therapy.
-
Comparative Analysis of CRISPR/Cas9 Delivery Methods in Marine Teleost Cell Lines.
Gene editing technologies such as CRISPR/Cas9 have revolutionized functional genomics, yet their application in marine fish cell lines remains limited by inefficient delivery. This study compares three delivery strategies-electroporation, lipid nanoparticles (LNPs), and magnetofection using gelatin-coated superparamagnetic iron oxide nanoparticles (SPIONs)-for CRISPR/Cas9-mediated editing of the ifi27l2a gene in DLB-1 and SaB-1 cell lines. We evaluated transfection and editing efficiency, intracellular Cas9 localization, and genomic stability of the target locus. Electroporation achieved up to 95% editing in SaB-1 under optimized conditions, but only 30% in DLB-1, which exhibited locus-specific genomic rearrangements. Diversa LNPs enabled intracellular delivery and moderate editing (~25%) in DLB-1 but yielded only minimal editing in SaB-1, while SPION-based magnetofection resulted in efficient uptake but no detectable editing, highlighting post-entry barriers. Confocal imaging and fluorescence correlation spectroscopy suggested that nuclear localization and Cas9 aggregation may influence editing success, highlighting the importance of intracellular trafficking in CRISPR/Cas9 delivery. Our findings demonstrate that CRISPR/Cas9 delivery efficiency is cell line-dependent and governed by intracellular trafficking and genomic integrity. These insights provide a practical framework for optimizing gene editing in marine teleosts, advancing both basic research and selective breeding in aquaculture.
-
A temperature-sensitive and less immunogenic Sendai virus for efficient gene editing.
UNLABELLED: The therapeutic potential of gene editing technologies hinges on the development of safe and effective delivery methods. In this study, we developed a temperature-sensitive and less immunogenic Sendai virus (ts SeV) as a novel delivery vector for CRISPR-Cas9 and for efficient gene editing in sensitive human cell types with limited induction of an innate immune response. ts SeV demonstrates high transduction efficiency in human CD34+ hematopoietic stem and progenitor cells (HSPCs) including transduction of the CD34+/CD38-/CD45RA-/CD90+(Thy1+)/CD49fhigh stem cell enriched subpopulation. The frequency of CCR5 editing exceeded 90% and bi-allelic CCR5 editing exceeded 70% resulting in significant inhibition of HIV-1 infection in primary human CD14+ monocytes. These results demonstrate the potential of the ts SeV platform as a safe, efficient, and flexible addition to the current gene-editing tool delivery methods, which may help further expand the possibilities in personalized medicine and the treatment of genetic disorders. IMPORTANCE: Gene editing has the potential to be a powerful tool for the treatment of human diseases including HIV, β-thalassemias, and sickle cell disease. Recent advances have begun to overcome one of the major limiting factors of this technology, namely delivery of the CRISPR-Cas9 gene editing machinery, by utilizing viral vectors. However, gene editing therapies have yet to be implemented due to inherent risks associated with the DNA viral vectors typically used for delivery. As an alternative strategy, we have developed an RNA-based Sendai virus CRISPR-Cas9 delivery vector that does not integrate into the genome, is temperature sensitive, and does not induce a significant host interferon response. This recombinant SeV successfully delivered CRISPR-Cas9 in primary human CD14+ monocytes ex vivo resulting in a high level of CCR5 editing and inhibition of HIV infection.
-
CRISPR/nCas9-Edited CD34+ Cells Rescue Mucopolysaccharidosis IVA Fibroblasts Phenotype.
Mucopolysaccharidosis (MPS) IVA is a bone-affecting lysosomal storage disease (LSD) caused by impaired degradation of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S) due to deficient N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity. Previously, we successfully developed and validated a CRISPR/nCas9-based gene therapy (GT) to insert an expression cassette at the AAVS1 and ROSA26 loci in human MPS IVA fibroblasts and MPS IVA mice, respectively. In this study, we have extended our approach to evaluate the effectiveness of our CRISPR/nCas9-based GT in editing human CD34+ cells to mediate cross-correction of MPS IVA fibroblasts. CD34+ cells were electroporated with the CRISPR/nCas9 system, targeting the AAVS1 locus. The nCas9-mediated on-target donor template insertion, and the stemness of the CRISPR/nCas-edited CD34+ cells was evaluated. Additionally, MPS IVA fibroblasts were co-cultured with CRISPR/nCas-edited CD34+ cells to assess cross-correction. CRISPR/nCas9-based gene editing did not affect the stemness of CD34+ cells but did lead to supraphysiological levels of the GALNS enzyme. Upon co-culture, MPS IVA fibroblasts displayed a significant increase in the GALNS enzyme activity along with lysosomal mass reduction, pro-oxidant profile amelioration, mitochondrial mass recovery, and pro-apoptotic and pro-inflammatory profile improvement. These results show the potential of our CRISPR/nCas9-based GT to edit CD34+ cells to mediate cross-correction.
-
Harnessing CRISPR/Cas-mediated genetic innovations in lepidopteran insects.
CRISPR/Cas-mediated genome editing of eukaryotic organisms gained immense popularity after the monumental publications made in 2012 and 2013 in heterologous editing of Escherichia coli and human kidney cells, respectively. In this regard, CRISPR/Cas has several important applications in agriculture, including gene-function validation and pest management. Recently researchers have contemplated employing this approach in achieving a chemical-free insect pest management strategy called 'genetic pest management'. In this approach both sex ratio and male sterility are achieved in one go by editing precisely the sex-determination genes and spermatogenesis-related genes. In vitro target gene validation is the key before taking up the final field application which is accomplished by employing ribonucleoprotein [RNP] complex combining guide RNA [gRNA] targeting specific regions and Cas protein which cuts the DNA at specific site/s followed by the error-prone repair by non-homologous end joining [NHEJ] resulting loss-of-function of the target gene. CRISPR/Cas-based genetic pest management possesses a lot of potential in Lepidoptera an important species order in Insecta and several globally significant pests. Therefore, the present review focuses on pertinent, up-to-date information on genome editing of the functional and phenotypic genes in Lepidoptera.
-
CRISPRoff epigenome editing for programmable gene silencing in human cell lines and primary T cells.
The advent of CRISPR-based technologies has enabled the rapid advancement of programmable gene manipulation in cells, tissues, and whole organisms. An emerging platform for targeted gene perturbation is epigenetic editing, the direct editing of chemical modifications on DNA and histones that ultimately results in repression or activation of the targeted gene. In contrast to CRISPR nucleases, epigenetic editors modulate gene expression without inducing DNA breaks or altering the genomic sequence of host cells. Recently, we developed the CRISPRoff epigenetic editing technology that simultaneously establishes DNA methylation and repressive histone modifications at targeted gene promoters. Transient expression of CRISPRoff and the accompanying single guide RNAs in mammalian cells results in transcriptional repression of targeted genes that is memorized heritably by cells through cell division and differentiation. Here, we describe our protocol for the delivery of CRISPRoff through plasmid DNA transfection, as well as the delivery of CRISPRoff mRNA, into transformed human cell lines and primary immune cells. We also provide guidance on evaluating target gene silencing and highlight key considerations when utilizing CRISPRoff for gene perturbations. Our protocols are broadly applicable to other CRISPR-based epigenetic editing technologies, as programmable genome manipulation tools continue to evolve rapidly.
-
CRISPR-edited babies arrived, and regulators are still racing to catch up.
-
CRISPR patent fight revived.
PubMed отдаёт не больше 10 000 первых результатов — уточните запрос, чтобы увидеть остальные.